Background: The purpose of this study was to analyze skeletal events unrelated to bone metastasis in men with castration-refractory prostate cancer (CRPC). Methods: A total of 68 patients with CRPC treated by secondary hormonal therapy (dexamethasone) and/or chemotherapy including docetaxel were analyzed. Primary endpoint was skeletal related events (SREs) after PSA relapse. PSA relapse was defined as 3 consecutive PSA increase and serum PSA more than 4 ng/ml. Zoledronic acid was given for 31 patients with radiographic bone progression from the initiation of docetaxel-based treatment. For 37 patients without radiographic bone progression, no bone targeted agents or radioisotopes were administered during the observation period. Results: During median observation period of 17.5 months (range 1 to 76 months), SREs were observed in 17 of 68 patients (25%). In patients with bone progression, SREs was observed in 8 of 37 (22%) patients, whereas 9 of 31 (29%) patients without radiographic bone progression experienced SREs unrelated to bone metastasis. All patients without radiographic progression had been treated by oral steroids (dexamethasone), which might be related to osteoporotic change in these cases. Conclusions: For CRPC patients without radiographic bone progression, caution needs to be paid for SRE unrelated to bone metastasis. The administration of steroids may cause osteoporotic change, thus preventive administration of anti-osteoporotic agents would be mandatory.